This Biomedical Research Partnership (BRP) proposal involves a partnership among a biomedical engineering team, a pulmonary physiology team, and a clinical pulmonary medicine team. This research program will incorporate state of the art optical engineering, advanced in vivo physiologic evaluation, and direct application to human obstructive lung diseases (OLD). Optical coherence tomography (OCT) is a technology capable of real time imaging of tissue microstructures in vivo, at micron scale resolution, and without ionizing radiation. Due to existing methodological limitations, this technology has not been utilized in any diagnostic or therapeutic venue related to OLD. To overcome these limitations, our partnership will develop and optimize a miniature OCT imaging probe and OCT imaging system. We hypothesize that high-resolution, high-speed, endoscopic OCT systems will allow identification and quantification of critical changes in tissue components in the airway wall that lead to OLD, and we will demonstrate the feasibility and evaluate the resolution of this endoscopic OCT platform in vivo in a canine model. We also hypothesize that this innovative technology can be applied to human lung disease to elucidate the etiology, progression of disease, and response to therapy in humans with OLD. We will demonstrate the efficacy of OCT in subjects with COPD and asthma. This innovative BRP proposal involves a working partnership involving state of the art optical engineering, advanced in vivo physiologic evaluation, and direct application to human lung disease. The biomedical engineering team will design and fabricate an ultrathin high-resolution OCT scanning endoscope systems at two wavelengths with an optimal working distance for accurately assessing thickness and fine structures of the airway walls in the peripheral small airways in vivo. The pulmonary physiology team will determine the accuracy of OCT resolution in vivo in small size canine airways. Finally, the clinical pulmonary medicine team will determine the correlations between the structural elements in the airway wall and the severity of OLD in humans. These works determines the mechanisms of OLD and enable future evaluations of new and existing therapeutic treatments by noninvasively quantifying their effects on airway wall structures and lung function.